Is LCA5 p.Arg237Ser (c.711A>C) pathogenic?

LCA5 p.Arg237Ser (c.711A>C) is classified Uncertain significance in LCA5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely pathogenic (0.7021); Absent from gnomAD v4.1; Associated with Leber congenital amaurosis 5.

What condition is associated with LCA5 p.Arg237Ser (c.711A>C)?

LCA5 p.Arg237Ser (c.711A>C) is associated with Leber congenital amaurosis 5 (ClinVar).

How common is LCA5 p.Arg237Ser (c.711A>C) in the general population?

LCA5 p.Arg237Ser (c.711A>C) is absent from gnomAD v4.1 (gnomAD).

How is Leber congenital amaurosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about LCA5 p.Arg237Ser (c.711A>C)?

AlphaMissense predicts likely pathogenic (score 0.7021) — an in-silico prediction, not a clinical call.

LCA5 p.Arg237Ser

c.711A>C · VCV4069763

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7021 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Leber congenital amaurosis 5

Computational evidence

Protein change
AlphaMissense	0.7021	likely pathogenic · top 8% in LCA5
REVEL	0.36	indeterminate
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.95, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 32 kb · p 0.58 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LCA5
Protein: p.Arg237Ser
Coding: c.711A>C
MANE Select: NM_001122769
Type: single nucleotide variant
Location: chr6:79513221 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.05

Full LCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

LCA5 p.Arg237Gly Uncertain significance ★ same residue
LCA5 c.190+1G>A Pathogenic/Likely pathogenic ★★ same condition
LCA5 c.721-1G>A Pathogenic/Likely pathogenic ★★ same condition
LCA5 c.721-2A>T Pathogenic/Likely pathogenic ★★ same condition
LCA5 c.858+1G>C Likely pathogenic ★★ same condition
LCA5 p.Ala319Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
LCA5 p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
LCA5 p.Arg255Ter Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/lca5-p-arg237ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown